Background People with schizophrenia exhibit notable difficulties in the use of everyday language, which directly impacts one's ability to complete education and succeed in employment. An impairment in the ability to understand and generate the correct grammatical structures (syntactic deficit) has been suggested as a key contributor; but studies have been underpowered, often with conflicting findings. It is also unclear if syntactic deficits are restricted to a subgroup of patients, or generalized across the broad spectrum of patients irrespective of symptom profiles, age, sex, and illness severity. Methods We conducted a systematic review and meta-analysis, registered on OSF, adhering to PRISMA guidelines, searching multiple databases up to May 1, 2024. We extracted effect sizes (Cohen's d) and variance differences (log coefficient of variation ratio) across 6 domains: 2 in comprehension (understanding complex syntax, detection of syntactic errors) and 4 in production (global complexity, phrasal/clausal complexity, utterance length, and integrity) in patient-control comparisons. Study quality/bias was assessed using a modified Newcastle-Ottawa Scale. Bayesian meta-analysis was used to estimate domain-specific effects and variance differences. We tested for potential moderators with sufficient data (age, sex, study quality, language spoken) using conventional meta-regression to estimate the sources of heterogeneity between studies. Findings Overall, 45 studies (n=2960 unique participants, 64.4% English, 79 case-control contrasts, weighted mean age(sd)=32.3(5.6)) were included. Of the patient samples, only 29.2% were women. Bayesian meta-analysis revealed extreme evidence for all syntactic domains to be affected in schizophrenia with a large-sized effect (model-averaged d=0.65-1.01, with overall random effects d=0.86, 95% CrI [0.67-1.03]). Syntactic comprehension was the most affected domain. There was notable heterogeneity between studies in global complexity (moderated by the age), production integrity (moderated by study quality), and production length. Robust BMA revealed weak evidence for publication bias. Patients had a small-to-medium-sized excess of inter-individual variability than healthy controls in understanding complex syntax, and in producing long utterances and complex phrases (overall random effects lnCVR=0.21, 95% CrI [0.07-0.36]), hinting at the possible presence of subgroups with diverging syntactic performance. Interpretation There is robust evidence for the presence of grammatical impairment in comprehension and production in schizophrenia. This knowledge will improve the measurement of communication disturbances in schizophrenia and aid in developing distinct interventions focussed on syntax - a rule-based feature that is potentially amenable to cognitive, educational, and linguistic interventions.
